Release of hormones and transmitters from endocrine cells and nerve endings is believed to occur by exocytosis. While the molecular basis of this process remains obscure, it is known that isolated secretory vesicles from adrenal medulla can be induced to release their contents by exposure to Mg++-ATP and permeant anions. This reaction is viewed as a model of chemical events leading to vesicle fusion with the plasma membrane and subsequent fission. We have found that vesicle release requires ATP, but that cleavage of the beta-gamma phosphate is not required. Thus, ATP binding, not hydrolysis, may mediate release. The consequence of ATP binding is a change in the transmembrane potential of the granule from negative to positive inside. This induces the osmotically inert core of the vesicle to dissociate and become osmotically active. Water enters the vesicle, and the vesicle "releases" by OSMOTIC SHOCK. This mechanism may also apply to cells. BIBLIOGRAPHIC REFERENCES: Pollard, H.B., Zinder, O., and Hoffman, P.G.: The Occurrence of Chromaffin Granules. Data Book on Cell Biology. P.L. Altman and D.D. Katz, eds. Fed. Am. Soc. Exp. Biol., publishers (1976) p. 359-362. Hoffman, P.G., Zinder, O., Bonner, W.M., and Pollard, H.B.: Role of ATP and Beta-Gamma Imino Adenosine Triphosphate in the Stimulation of Epinephrine and Protein Release from Isolated Adrenal Secretory Vesicles. Archives of Biochem. Biophys. 176: 375-388, 1976.